Benchmarking cartilage regeneration across ten chondrogenic cell sources using native tissue references

Ponta, S.; Pecina, V.; Airoldi, M.; Simmen, D.; Novoa Olivares, E.; Linder, T.; Laurent, A. E.; Applegate, L. A.; Salzmann, G.; Bruhin, V.; Stoddart, M.; Zenobi-Wong, M.; Fisch, P.

doi:10.64898/2026.10.05.756631

bioRxiv · 10.64898/2026.10.05.756631

Benchmarking cartilage regeneration across ten chondrogenic cell sources using native tissue references

Ponta, S.·Pecina, V.·Airoldi, M.·Simmen, D.·Novoa Olivares, E.·Linder, T.·Laurent, A. E.·Applegate, L. A.·Salzmann, G.·Bruhin, V.·Stoddart, M.·Zenobi-Wong, M.·Fisch, P.

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Abstract

A persistent challenge in cartilage tissue engineering is identifying cell sources capable of regenerating cartilage with native-like properties. Variability in chondrogenic potential among human- and animal-derived cells complicates graft development and disease modeling. Here we benchmarked ten chondrogenic cell sources under standardized culture conditions using hyaluronan-alginate biomaterials and implementing a functionality index combining histological and mechanical metrics referenced to native tissue. Mesenchymal stem cells and fetal chondroprogenitors demonstrated superior regenerative capacity, achieving 103% and 95% of native cartilage functionality, respectively. In contrast, adult articular chondrocytes from healthy and osteoarthritic donors produced fibrocartilaginous tissue with functionality scores below 50%. These findings provide a quantitative framework to guide cell source selection and optimize cartilage graft standardization for clinical applications and physiologically relevant disease models, addressing regulatory demands for product characterization.

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Ponta, S., Pecina, V., Airoldi, M., Simmen, D., Novoa Olivares, E., Linder, T., Laurent, A. E., Applegate, L. A., Salzmann, G., Bruhin, V., Stoddart, M., Zenobi-Wong, M., Fisch, P.. 2026-10-06. Benchmarking cartilage regeneration across ten chondrogenic cell sources using native tissue references. https://doi.org/10.64898/2026.10.05.756631

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